Please note, this event is being recorded. I will now turn the call over to Tram Bui, Halozyme's Vice President of Investor Relations. Please go ahead.
Thank you, operator. Good afternoon, and welcome to Halozyme's Third Quarter 2026 Financial and Operating Results Conference Call. In addition to the press release issued today after the market close, you can find a supplementary slide presentation that will be referenced during today's call in the investor relations section of our website.
Leading the call will be Dr. Helen Torley, Halozyme's President and Chief Executive Officer, who will provide an update on our business, and Darren Snellgrove, our Chief Financial Officer, who will review our financial results and outlook.
On today's call, we will be making forward-looking statements as outlined on slide two. I would also refer you to our SEC filings for a full list of risks and uncertainties. During the call, both GAAP and non-GAAP financial measures will be discussed. Certain non-GAAP or adjusted financial measures are reconciled with the comparable GAAP financial measures in our earnings press release and slide presentation.
I will now turn the call over to Dr. Helen Torley, and we will start on slide three.
Thank you, Tram, and good afternoon, everyone. I am pleased to report another exceptionally strong quarter for Halozyme, as more patients, physicians, and healthcare systems experience the benefits of subcutaneous delivery with ENHANZE. This is reflected in the record total and royalty revenues. Operationally, we continue to demonstrate new growth opportunities resulting from our compounding platform engine, ENHANZE. In and post the quarter, we significantly expanded the ENHANZE opportunity, with three current partners expanding their agreements to add four new target nominations. Additionally, three ENHANZE-enabled programs, one each from Pfizer, Incyte, and argenx, advanced into phase I development. GSK plans to initiate a phase I-B study of a subcutaneous formulation of belantamab with ENHANZE. With this planned start, we are on track to achieve 13 ENHANZE programs in clinical development by year-end.
Importantly, we also advanced our two hyperconcentration technologies, Hypercon and Aerocon, the new name for Surf Bio, moving these closer to clinical testing. All of this contributed to the record total revenue, royalty revenue, and adjusted EBITDA for Q3. Total revenue increased 39% year-over-year to $493 million, driven by royalty revenue, which increased 44% to a record $341 million. These results reflect the continued growth of our established commercial partner product portfolio and the growing contributions from the newer launches, which is resulting in a diversified and growing set of royalty revenue streams. Profitability remained strong during the quarter, with adjusted EBITDA of $336 million and an adjusted EBITDA margin of 68%, reflecting our disciplined execution. Based on this strength, we are raising our full-year 2026 financial guidance. Darren will be discussing this in greater detail.
Turning to slide four, let me now say a few more words about how we are increasing the ENHANZE opportunity through expanded agreements and new nominations by current partners. Three current ENHANZE partners expanded their collaborations and nominated four additional targets. argenx expanded their agreement to include two additional exclusive targets, bringing the total to eight. Incyte expanded and added one additional target to evaluate subcutaneous axatilimab. In October, Johnson & Johnson added an additional oncology target to its longstanding ENHANZE collaboration. Collectively, these four new nominations expand the opportunity, further diversify our partnered pipeline, and add new potential sources of milestone and royalty revenue.
Let me now move to slide five, and I'll provide some performance highlights on our commercial ENHANZE portfolio. DARZALEX subcutaneous, VYVGART Hytrulo, and Phesgo have all continued to demonstrate strong royalty revenue growth. In addition to and on top of this, Ocrevus Zunovo, OPDIVO Qvantig, and RYBREVANT FASPRO are adding increasingly meaningful royalty revenues. ENHANZE provides a competitive advantage for our partners by improving convenience, reducing administration time, and in some cases, improving the safety and tolerability profile compared to the IV treatment. For multiple partner products, these benefits are resulting in strong growth as the SC enables new sites of care and increase access to and for patients.
I'll begin with highlights on the newer launch products. Roche continues to report strong momentum for subcutaneous Ocrevus Zunovo , with approximately 56,000 patients globally now receiving the 10-minute subcutaneous formulation, an increase of about 12,000 patients since the first half of the year. Global conversion from OCREVUS IV to subcutaneous has now exceeded 20%, with adoption driven by both conversion and, importantly, new patients starting on Ocrevus Zunovo .
Roche noted on their third quarter call that approximately 50% of the Ocrevus Zunovo starts are patients naive to OCREVUS treatment. This, I believe, demonstrates expansion of Ocrevus Zunovo into community and more rural treatment settings where IV capacity can be limited. Roche continues to expect high single-digit OCREVUS growth in 2026 and CHF 9 billion , or approximately $11 billion, in peak franchise sales by 2029. At just over 20% conversion to date, and with royalty revenues to at least 2034, this represents a large opportunity for Halozyme.
I'll move now to Bristol Myers Squibb and OPDIVO Qvantig. On its third quarter call, BMS reported that approximately 17% of the OPDIVO IV business has already converted to OPDIVO Qvantig, which is the subcutaneous formulation, with uptake occurring across multiple tumor types. Importantly, they also commented that conversion is tracking towards the higher end of its expectation for 30%-40% of the IV business to ultimately convert to the subcutaneous formulation. SC administration with ENHANZE is delivering meaningful benefits for patients and physicians, including improved practice efficiency and a more convenient treatment experience. With durable royalties projected for many years and significant conversion ahead, this also represents an attractive growth royalty stream.
Johnson & Johnson's RYBREVANT FASPRO is another exciting opportunity. J&J reported 63.5% growth of RYBREVANT plus LAZCLUZE in the third quarter, driven by strong share gains in both first and second-line lung cancer treatment, continued launch uptake across regions, and rapid adoption of the subcutaneous version, RYBREVANT FASPRO. They further noted that they expect FDA approval of RYBREVANT FASPRO in advanced head and neck cancer by the end of 2026, which would expand the opportunity beyond lung cancer into another area of significant unmet need. Johnson & Johnson also highlighted that RYBREVANT is one of their key newer products that is expected to contribute more meaningfully to future growth, and have commented that this growth will be fueled by RYBREVANT FASPRO. This represents another growth royalty revenue stream for Halozyme, with royalty revenues projected to the late 2030s.
I'll now move to DARZALEX subcutaneous, VYVGART Hytrulo, and Phesgo. I'll begin with DARZALEX. J&J reported $4.2 billion in sales in the third quarter for DARZALEX, reflecting operational growth of 15.6%. Virtually all of the DARZALEX reported sales are for the DARZALEX subcutaneous version with ENHANZE. This strong performance was driven by continued share gains across all lines of therapy, including 10 points of share gain in the frontline setting, together with ongoing market expansion. With analysts now projecting sales of $21 billion in 2028, we are excited to support the continued growth and expansion of this exceptional product.
I'll move now to VYVGART Hytrulo. argenx reported total VYVGART sales of $1.7 billion in the quarter, impressive growth of 54% year-over-year and 13% sequentially. argenx highlighted continued growth in both generalized myasthenia gravis and CIDP, which is driven by the VYVGART Hytrulo prefilled syringe that provides greater patient convenience and flexibility in how treatment is administered. A recent additional driver of growth is the approval for seronegative myasthenia gravis, which is already broadening their prescriber base, with approximately 10% of seronegative prescribers new to VYVGART.
Further opportunity expansion is projected in 2027, with potential approvals in ocular and pediatric myasthenia gravis. Beyond myasthenia gravis and CIDP, argenx is seeking to expand into a new population of patients, those with immune-mediated necrotizing myositis, or IMNM, with a sBLA planned by year-end. This is a high unmet need patient population, where argenx has estimated there are approximately 20,000 patients living with this disease in the United States alone. These opportunities reinforce the potential for VYVGART Hytrulo to continue expanding across indications, patient populations, and prescribers, delivering long-term growth and projected royalty revenues to Halozyme into the 2040s.
Moving now to Roche's Phesgo. In the third quarter, Roche reported that Phesgo also continued to deliver strong performance, with global conversion reaching 59%, up 5 percentage points since mid-year, signaling continued strong adoption for a product that was launched six years ago in 2020. The continued conversion from Perjeta reinforces the durability of Phesgo, with royalties projected into the 2030s, and the value of ENHANZE in enabling sustained adoption of subcutaneous therapies. Collectively, all six products are demonstrating the continued scalability and durability of ENHANZE. Our established products continue to deliver strong growth, our newer launches are becoming increasingly meaningful contributors, and the ongoing clinical, regulatory, and commercial progress are providing multiple drivers for future revenue growth.
Moving now to slide six. With the new study starts in the third quarter, we have significantly expanded our product development pipeline. To date, we have 12 ENHANZE programs in clinical development, three of which the partners have requested to keep confidential at this time. With GSK planning to initiate a phase I-B study of a subcutaneous formulation of belantamab with ENHANZE, we are on track to reach 13 clinical stage programs by year-end 2026.
Recent advancements to highlight are Pfizer's initiation of a phase I study of tilrekimig, their investigational potential first-in-class trispecific antibody that simultaneously inhibits upstream and downstream drivers of type 2 inflammation. Also, Incyte's initiation of a phase I study evaluating a subcutaneous formulation of their first-in-class antibody designed to selectively target mutant calreticulin. Finally, argenx's evaluation of ARGX-119, their first-in-class humanized agonist monoclonal antibody targeting MuSK.
Importantly, multiple partners are moving programs from collaboration signing into the clinic rapidly within months of signing. This momentum is a strong reflection of a broader trend in biopharmaceutical companies focusing on subcutaneous administration. Subcutaneous delivery is now recognized not simply as a convenience feature, but as an important driver of patient preference, healthcare system efficiency, competitive differentiation, and market expansion. This pace of execution, combined with attractive opportunities across oncology, immunologies, and multiple other therapeutic areas, represents a highly attractive set of opportunities for ENHANZE royalty revenue beginning in the 2029+ period and extending well into the next decade.
This is the compounding platform engine at work. Commercial success driving new partner demand, new agreements creating additional development programs, and those programs building the next waves of potential royalty revenue. An important additional benefit of our compounding platform engine is the continuous innovation that is generated as we work with partners across a growing range of molecules, formulations, and delivery challenges. I am pleased to report that collaboration patents have been obtained by our licensees for seven of the 10 launch products, and that collaboration patents are pending for the others. We continue to expect that new collaboration patents will be granted to protect our licensees' innovations as they generate new data from their clinical trials.
Let me now move to MDASE and our modified hyaluronidase IP portfolio. Halozyme pioneered and invented the use of hyaluronidases for large volume subcutaneous delivery. On October 7, 2026, the specialized Dutch Patent Court of The Hague rejected Merck's invalidity challenges against Halozyme's MDASE patent EP622 and found KEYTRUDA QLEX to be infringing the patent. The court also found that there was no reasonable likelihood that EP622 will be declared invalid in the other relevant European member states where EP622 is granted, and prohibited Merck's European marketing authorization holder from committing an infringement in Belgium, Denmark, France, Ireland, Italy, Sweden, Switzerland, and the Netherlands by manufacturing or causing to be manufactured, offering, putting on the market, or using KEYTRUDA subcutaneous in those countries, or by importing it or holding it in stock for that purpose.
Previously, in December of 2025, Halozyme won a critical preliminary injunction in Germany for EP622. The Munich Regional Court ordered Merck to halt the launch and distribution of KEYTRUDA QLEX in Germany. In February of 2026, the German Federal Patent Court issued a preliminary opinion in validity proceedings that were brought by Merck, finding that Halozyme's EP622 patent is likely valid. Together, these rulings prevent Merck from launching KEYTRUDA QLEX in key European markets and prevent Merck from achieving the same adoption and trajectory of KEYTRUDA QLEX in Europe as they are doing in the U.S. I want to underscore just how important these recent EU court decisions are in supporting the validity of our EP622 patent and supporting Halozyme's position as the pioneer and leader for innovating the use of human-derived hyaluronidases for large volume subcutaneous administration.
I'll now move to Hypercon and Aerocon, our hyperconcentration technologies. Hypercon and Aerocon are complementary technologies to ENHANZE that extend our leadership in subcutaneous drug delivery, expand our addressable opportunity, and will create additional long-term royalty opportunities for Halozyme. Each has been demonstrated to achieve stable formulations of biologic therapies at a concentration of approximately 500 milligrams per mL, which is three to fourfold what is commonly achieved. The resultant lower volume required can allow delivery using a small volume auto-injector at home or in the doctor's office, with the potential to further improve the patient treatment experience.
To date, five collaboration and licensing agreements have been signed for access to Hypercon, including the potential to use Hypercon with more than 20 potential targets or drugs. We are on track to complete the clinical supply for two partner products formulated with Hypercon in the first quarter of 2027 to support first half 2027 phase I trial initiations. In parallel, we're advancing the Hypercon formulation for a growing portfolio of development programs, including both commercial stage and development stage assets, with several programs originating from recently signed collaborations and others representing future collaboration agreement opportunities.
Now a word on Aerocon. We're on track with our plans for 2026, which continue to support new deal signings in 2027 and clinical entry in the second half of 2028. With Halozyme's deep expertise, established capabilities, and proven track record in drug delivery, Halozyme is the natural home for innovative drug delivery technologies.
I'll now pass the call over to Darren, who will be discussing our financial results, updated outlook, and capital allocation.
Thank you, Helen. I will start on slide seven. The third quarter was another exceptional quarter for Halozyme. We delivered record royalty and total revenue, strong earnings growth, and substantial cash flow generation while continuing to advance our future growth opportunities. Our results reflect the increasing diversification of our royalty portfolio, with continued outperformance of our established commercial products and growing contributions from newer launches. Combined with the ongoing advancement and expansion of our pipeline, this supports the long-term durability of our revenue. We also successfully completed a $1.5 billion convertible note offering on attractive terms. The transaction reflects the strength of our financial profile and confidence in our long-term outlook, while further strengthening our balance sheet.
Turning to the third quarter results, total revenue increased 39% to $493 million, compared to $354.3 million in the prior year period. This performance was driven by robust royalty revenue growth and higher product sales.
Moving to slide eight for more details on royalty revenue. Royalty revenue increased 44% year-over-year to a record $341 million, reflecting continued strength across our commercial portfolio. Third quarter DARZALEX royalty revenue increased 20% year-over-year to $153.5 million. VYVGART royalties to Halozyme increased 89% year-over-year to $88.1 million. Phesgo royalty revenue increased 23% year-over-year to $34.3 million in the third quarter. Other royalty revenue increased 92% to $65.1 million, driven by growing contributions from Ocrevus Zunovo , OPDIVO Qvantig, RYBREVANT FASPRO, and TECENTRIQ HYBREZA.
Moving to slide nine for additional details on profitability and our balance sheet. Research and development expenses were $27.8 million compared to $17.3 million in the prior year period, reflecting continued investment in advancing our ENHANZE and next-generation technology platforms. Selling, general, and administrative expenses were $58.2 million in the quarter, compared to $46.1 million in the prior year period.
The increase in SG&A expenses was primarily due to an increase in consulting fees, including litigation costs related to Merck. Net income increased 41% to $247 million from $175.2 million in the prior year period. Adjusted EBITDA increased 35% to $336.2 million from $248.2 million in the prior year period, driven by continued strong royalty growth. GAAP diluted earnings per share was $2.01 compared to $1.43 in the prior year period. Non-GAAP diluted earnings per share was $2.39 compared to $1.72 in the third quarter of 2025.
Moving to slide 10. Our capital allocation priorities are unchanged. We remain focused on investing in the highest return opportunities across ENHANZE, Hypercon, and Aerocon, maintaining a strong balance sheet, and returning excess capital to shareholders through a disciplined capital return framework. Consistent with this approach, we completed $400 million of share repurchases in 2026. We also remain focused on deleveraging, including addressing our 2027 and 2028 convertible notes at maturity.
Our net leverage was 2.4x. We ended the quarter with $1.08 billion in cash equivalents, and marketable securities, and $3.3 billion of long-term debt, leaving us well-positioned to fund our organic growth initiatives while maintaining significant financial flexibility. Beyond our organic investments, we will continue to evaluate selective strategic opportunities that complement our portfolio and meet our discipline criteria for strategic fit, durable value creation, and attractive returns.
Moving to slide 11. Based on our performance through the first nine months, we are raising our 2026 financial guidance. We now expect total revenue of $1.86 billion-$1.925 billion, an increase of $20 million at the midpoint, representing growth of 33%-38% over 2025. Within that, we now expect royalty revenue of $1.235 billion-$1.255 billion, up $12.5 million at the midpoint, representing growth of 42%-45%. Royalties remain the engine of our business and the main driver of this raise.
We now expect product sales of $525 million- $540 million, up $7.5 million at the midpoint. We are raising adjusted EBITDA to $1.24 billion- $1.29 billion, up $12.5 million at the midpoint, with our adjusted EBITDA margin unchanged at approximately 67%. Finally, we now expect non-GAAP diluted EPS of $8.75-$9.05, up $0.08 at the midpoint. The updated outlook reflects the continued strength of our diversified royalty portfolio, substantial operating leverage, and strong cash generation. With that, I'll turn the call back to Helen.
Thank you, Darren. In closing, our third quarter performance demonstrates the strength of our compounding technology platform ENHANZE, where the actions during and post this quarter added meaningful near and long-term value. Hypercon and Aerocon share many similar features and will create two additional compounding platforms on top of ENHANZE.
Let me leave you with four key takeaways. Firstly, our royalty portfolio continues to grow and diversify. Record royalty revenue and growing contributions from three more recently launched products demonstrate the increasing breadth and durability of our business. Secondly, demand for ENHANZE remains exceptionally strong. The expanded agreements with existing partners will add multiple new programs into the development portfolio, with the potential to broaden the reach of ENHANZE and create new royalty revenue streams. Thirdly, we're growing the next wave of royalty opportunities. We're on track to add 13 ENHANZE programs in clinical development by year-end. Hypercon also remains on track for its first clinical trial start in the first half of 2027. Finally, our strong cash generation and financial flexibility provide additional capacity to invest in our technologies while maintaining a disciplined approach to capital allocation.
Each new royalty stream, future launch opportunity, and partnership adds another layer of growth on top of the foundation we have already built. I thank you all for your time today, and operator, you can now open the call for questions.
We will now begin the question-and-answer session. If you would like to ask a question, please press star one to raise your hand. To withdraw your question, press star one again. We ask that you pick up your handset when asking a question to allow for optimum sound quality. If you are muted locally, please remember to unmute your device. Please stand by while we compile the Q&A roster. Your first question is from Jason Butler with Citizens JMP. Your line is now open. Please go ahead.
Hi. Thanks for taking the questions, and congrats on the quarter. Helen, now that you're several quarters past the last two acquisitions, what do you think your capacity is to bring in more synergistic technologies, and what's your kind of perspective on priority there? Then I have a follow-up. Thanks.
Yeah. If it's okay, Jason, I'll ask Darren to address that.
Yeah. Thanks for the question, Jason. For M&A, what I'd say is that our two recent acquisitions, Hypercon and Aerocon, are progressing well, and so those are important growth drivers for us to continue to invest behind. The good news is both our organic opportunities and our financial position are strong, so that really gives us the patience to be disciplined as it relates to M&A and act really only when we can find a deal that can clearly improve the long-term outlook.
So, we would expect a new deal to really be something that would expand the drug delivery portfolio, something that could extend our royalty duration or strengthen the long-term revenue outlook. Obviously, it needs to meet the appropriate return threshold. So we're definitely interested in technology that complements our platforms that can be deployed through scalable partnerships. That is really what we are looking for.
Great. Thank you. In terms of the hyperconcentration technologies, when you are speaking to prospective partners, what are they looking for in terms of technical proof of concept to move forward with a program, and when do you think we will have the initial data from established partnerships that could provide that initial proof of concept?
Yeah. I think there are two kind of elements of proof of concept, Jason, to think about. One is the actual formulation. Can you formulate the product into a hyperconcentrated product? As you know, we have got multiple examples, and very successful examples, of doing that up to 500 milligrams per ml. What we are finding is for some companies, they want to see it first, and other companies, they will accept the fact it is going to be very possible based on the wealth of data we already have. So I think that is one.
On the call, I mentioned we have got multiple people in feasibility testing. Some of them are partners who signed before. The early development testing does encompass that formulation testing. Some of that is our current partners, and some of it is people who want to get that data before they move forward to a new agreement. We actually have a little bit of a pipeline of potential future agreements in that group of companies who are testing the formulation.
I think the next proof of concept is the clinical proof of concept. The companies that are most advanced and we expect to be in the clinic in the first half of 2027 have done the preclinical data. They have done all of that testing they can do. The next real step that they want to see is the clinical data. We are excited to be supporting them and moving forward to these phase I studies that will evaluate PK, local tolerability, things like that. So, those would be the two things, but everything is advancing exactly as we had expected, and we are looking forward to starting the clinical studies in 2027.
Great. Thanks for taking the question.
Your next question is from Michael DiFiore with Evercore ISI. Your line is now open. Please go ahead.
Hey, guys. Thanks so much for taking my question, and congrats on all the continued progress. Another question from me on Hypercon. Helen, what's the most important assumptions driving the $1 billion Hypercon royalty opportunity, and how much of that opportunity depends on established molecules just undergoing a formulation bridge versus investigational molecules that still need to demonstrate efficacy. Thank you.
Yeah. As we put out that projection that we can achieve $1 billion, we were looking at an expectation of having five to seven products that would be in the clinic before the mid-2030s for that, Mike. That does include majority of those products already are clinically de-risked in terms of already being launched products. But there are some exciting earlier stage products that we do anticipate have the potential to launch by that time as well. But a heavy skew to already successful commercial products.
Thank you.
Your next question is from Mitchell Kapoor with H.C. Wainwright. Your line is now open. Please go ahead.
Hi, this is Amitan for Mitchell. Thank you for taking our question, and congrats on a strong quarter. For subcutaneous belantamab, is the phase I-B study designed primarily to establish PK comparability, or are you also looking at peak exposure and how that improves safety? I think one thing that we're interested in is which toxicities do you believe could improve? I have a quick follow-up. Thank you.
Yes. I don't believe GSK has posted a lot of details with regard to this study, so what I will be able to do is just speak in generalities about where we believe that ENHANZE is going to be able to be impactful with antibody drug conjugates. Phase I studies often evaluate the pharmacokinetics, and that's exactly what I would expect in this case. I do believe we'll be looking at the absorption profile, identifying is the Cmax coming down with ENHANZE versus perhaps what's historically been seen with IV, but also what is the overall exposure, which does correlate generally very well with efficacy. So, that, in general terms, is what we would expect for them to be looking at.
Again, speaking in generalities, we are talking with broad partners, Cmax-related toxicities can be anything from low white cell counts to GI distress to even ocular challenges as well. So, each ADC that we work with is going to be different in terms of what the partner is seeking to mitigate potentially with the change in the profile. Some are very much just focused on, though, getting to an even stronger overall risk-benefit profile, perhaps being able to even dial up the efficacy a bit with a higher exposure. So, each partner has got different objectives, and we look forward to GSK sharing their objectives at some later date.
Got it. Thank you. I guess with additional targets being committed to existing partners, what obligations or what are the dynamics and deadlines accompanying ENHANZE exclusivity? When can Halozyme recover a target, for example, if that partner does not advance it?
Yeah, we have been in a very fortunate position that most of our partners, when they take exclusive targets, have advanced them or are advancing them. There have been instances, rarely over the years, where perhaps a product has not progressed in the clinic or had the efficacy that was expected. I will say in those instances, as soon as the company made a decision not to move forward with that target, they have returned it to Halozyme. So, that is generally the structure of our agreements.
Got it. Thank you.
Your next question is from Sean Laaman with Morgan Stanley. Your line is now open. Please go ahead.
Hi, Helen and team. Congratulations on the numbers, and hope everyone's well. Helen, on slide six, when you're talking through those new products, new pipeline products, which are largely in phase I, how should we think about those as potential contributors post the commencement of reduced royalty rates? I assume some of these partners, the royalty rate reduces in line with some of your existing marketed products. Then I have a follow-up.
Yeah. The way we think about that portfolio, Sean, is very much one that what's exciting about it is the breadth of products that are in there. There is a mix of already established commercial products, but we're also very proud to be working with partners who are trying to move forward true innovations in care and not just me-toos. If we, on the call, I happened to mention Pfizer's trispecific tilrekimig, which is going to make a big difference, we believe, in patients with type 2 inflammation. So, think of it as an exciting and broad portfolio.
The deal structures are all a little bit different in some of our more recent deals, some of which are represented on that chart. We have a deal structure where it starts in the low single-digit royalties, going up into the mid-single-digit royalties. But in that instance, there is a modest reduction in the royalty rate if there are no valid patents.
So, it's a very wide range of opportunities, but the message we have is exciting products, big TAM represented by these products, durable royalties, with many of them going into the 2040s, we project, and not all of them having step downs depending on if they get co-form patents, which we believe many of them will get. This is why we talk about the great value of our compounding platform engine, because we're able to just keep adding wave upon wave of attractive royalties.
Interesting. Thank you. I have a question on KEYTRUDA QLEX. According to the FDA approval letter for KEYTRUDA QLEX, the finished product is manufactured and filled by, I think it's BSP Pharmaceuticals in Italy, which appears to be the only FDA-approved facility for this purpose. I think the October 7th Dutch injunction prohibits Merck's Dutch subsidiary from manufacturing or arranging manufacturing in the affected countries, as well as facilitating infringement by its affiliates. I'm just wondering, the injunction does not appear to distinguish between manufacturing for sale in those countries and manufacturing for export elsewhere. Would it be right to potentially assume that it affects Merck's ability to supply QLEX to the U.S. and other markets outside the scope of the injunction?
Yeah. We can't address the potential impact on U.S. supply, as we don't have full knowledge of Merck's worldwide supply chain. Let me just take a step back and talk about what the Dutch court prohibited, just to provide a little bit of context and tell you where the prohibition is.
The ruling from the Dutch court did stop Merck's EMA holder and its affiliates from committing an infringement in multiple European countries, as you know, including though by the manufacturer causing KEYTRUDA QLEX to be manufactured in those countries. As you mentioned, we know that BSP Pharmaceuticals in Italy is a manufacturer for QLEX for Merck. The current prohibition by the court that's in place for Merck's MA holder and its affiliates, we believe, does impact those entities' ability to supply QLEX from BSP entity, regardless of the ultimate destination of the product. That's an important distinction there.
I will say Halozyme has also taken some additional actions and has sued BSP directly for infringement of EP622. So it's clear around the EMA holder, its affiliates, and what we know about BSP Pharmaceuticals, cannot comment on U.S. supply.
Got you. Extremely helpful on both questions. I appreciate it.
Your next question is from Dave Risinger with Leerink Partners. Your line is now open. Please go ahead. Hi there, Dave. Your line is now open. You can go ahead with your question.
Sorry about that. Thanks very much for all the updates today, and nice to see the progress. I guess I wanted to start on Hypercon. Helen, could you just comment on whether there's any change today in the expected timing of two potential phase I starts in 2027? I think you mentioned the first half of 2027. I do not know if both were previously expected to start in the first half. I just cannot recall. Then, second, with respect to one other Hypercon question, then I have one more, please. The second Hypercon question is, could you talk about scale-up? I know that it has been somewhat challenging to scale up Hypercon. Could you address that, please? Thank you.
Yeah, Dave, there is no change recently in our timeline of the expectation of when we would have the first clinical starts. Much earlier this year, we had stated that we expected now that the first clinical starts would be in the first half of 2027, and that is where we are tracking. I mentioned on the call, we are expecting to make our first clinical supplies for the first two partners in the first quarter to support the starts during the first half of 2027.
With regard to the scale-up, any novel project like this does come with the need to evolve it as you are going on. I have to say, we have been making very, very strong progress with that, and that is what gives me confidence in supply. The team has done a super job going from bench scale into now being just quarter and a bit away from the actual scale-up to clinical supply. Obviously, that was incredibly important as a milestone for us to be able to support the new clinical starts.
Once we have done that, we have to start thinking about commercial launch and commercial supply. That is where we are very hard at work at the moment, finding additional partners to be able to do that process. But we expect that to be a very straightforward process, because the hard work happens between your bench and your first clinical scale-up, because all that the commercial scale-up will be, will be a slightly bigger volume, but it will use largely the identical process. Really pleased with the progress and success that we are having there, and look forward to keeping you updated.
Great. Thank you. The other one relates to the Merck litigation. I think many observers have been surprised that Merck hasn't settled with Halozyme to be able to introduce its subcutaneous KEYTRUDA in Europe. I'm guessing that if the company is having conversations with Merck, that it may relate to not just European litigation, but also U.S. litigation. My two questions are, first, could you compare and contrast your success in Europe versus your lack of success to date in the U.S., and comment specifically on that patent that blocked Merck in Europe? Then second, where are you with respect to having conversations with Merck? Thanks very much.
Yeah, I'll take the second part first, Dave. We haven't engaged in any conversations with Merck, and obviously, if we did do that, we wouldn't be in a position to provide any updates on that. Let's talk about where we are in Europe. We're absolutely thrilled with the resounding win from the Dutch court, which not only found that Merck was infringing, and this was a final decision after a full trial. They were found to be infringing on October 17, and importantly, the court also said at that time that there's no reasonable likelihood that EP622, which is that key European patent, will be declared invalid in any other relevant European member states where EP622 is granted.
Why do I emphasize that? I emphasize that because that really supported the court's decision to have this broad restriction from launching in eight of the European markets. As you know, we already have an injunction in Germany as well. This EP622 is distinct from the U.S. patent portfolio, and we're very pleased with the recognition by the European, and particularly the Dutch and German patent courts, on the validity of our patent and the fact that we are being infringed. It's important because, as we look at Europe, those eight markets and nine markets, including Germany, in our experience from the subQ market, represent about 20% of total global royalties. So, we think this was a very important win strategically for Halozyme.
If we move to the U.S., to date, yes, Merck has been successful in gaining initial rulings on our U.S. patents, which, as I say, are distinct. We've received adverse validity decisions on multiple of our PGRs that were filed. However, we are very confident that as we move forward into an appeal process here, which will take likely until 2028, that we will prevail. There's a lot of facts behind that statement, Dave, but it really comes from us being the pioneer in this area, and we believe that the appeal court will recognize just how strong our case is in terms of that. So, very different patent systems, different patents in each of these. We do expect over time we're going to reap the same success in the U.S. as we have seen in Europe to date.
Thank you.
Your next question comes from Brendan Wiatrowski with TD Cowen. Your line is now open. Please go ahead.
Hi, guys. I think that is supposed to be me, Brendan. Sorry for the confusion there. Thanks for taking the questions. Appreciate all the color on, especially the progress, kind of the next wave of ENHANZE assets. I did notice kind of higher bulk API sales for the ENHANZE enzyme itself this quarter, which presumably will continue to ramp, I guess, as more drugs move through the clinic, I guess, this and next year. Helen, can you just remind us, how should we think about kind of the comparable revenue contribution from Hypercon as those assets move into and through the clinic? I think it is more milestone-based rather than API sales, but I guess how material could those be next year as the first couple Hypercon drugs start phase I?
I guess just secondly, related to that, are there any updates on when you might expect kind of the third and fourth Hypercon drugs to enter the clinic after those first two start on the first half of next year? Thanks.
Yeah, you are quite right, Brendan, that for Hypercon, we won't be seeing API revenue. We'll see a small amount of collaboration revenue as we do experiments and partners pay for that work and our FTEs, but it's not the same model in terms of the API, so don't expect a line in API. But the model is very similar to our ENHANZE profile that you've seen for the 10 approved products, where as a product is progressing to become more and more de-risked, there are escalating milestones. So, phase III is usually substantially higher than a phase I milestone. There are meaningful milestones at approval, and then milestones as products achieve certain sales thresholds. So, very similar, and it can, you are quite right, be a meaningful contributor to our milestone revenue over time.
With regard to products three and four, I mentioned that we are very pleased with the progress we're seeing and how broad the development pipeline is. We don't have specific dates from those partners as to when they will be moving into the clinic, but we can say numbers three and four are getting teed up, and we'll look forward to providing an update when those clinical start dates are more clear to us.
Great. Thanks. If I could just quickly follow up. I know you've in the past, I think, flagged, I think, 13 new launches between 2029 and 2031. I guess, can you first confirm if that's still what we should expect in terms of the number and timing of that next wave? But then also if the 13 ENHANZEs you're flagging here in the deck to be in the clinic by the end of this year, are those kind of the same 13 or if there's any other maybe new indications or Hypercon included in that 2029 to 2031 timeframe? Thanks.
Yeah. The 13 products are all new molecular entities in terms of what we count. We actually will have other new indications launching, Brendan, particularly as an example on VYVGART that continues to just add and expand. Those aren't on the list, so that is not considered. This is actual new products moving into the clinic.
We have said, yes, up to 13 of these will launch between 2029, and I do believe it was more 2032, but it is going to be in that window if they follow, and we would expect them to, our usual timeline for development, which is anything from four and a half to five and a half years. So, that's what's giving us that confidence in that window. Now, obviously, they have to advance in development, but up to 13 is exactly the number.
Got it. Sounds good. Thank you.
Your next question is from Jessica Fye with JPMorgan. Your line is now open. Please go ahead.
Hey, guys. Good afternoon. Thanks for taking my question. Maybe coming back to Hypercon, you've mentioned for a couple quarters now that a Hypercon partner is evaluating the potential return of a target. Just talk us through what are various reasons that partners return targets? The second one is, what's the viscosity that you're seeing with the Hypercon-formulated products? This may just vary by product, but is there any upper bound that you want to stay under, and are you finding that you're able to do that thus far? Thank you.
With regard to Jess, I'll talk broadly on this as to why a partner might choose to return a target. It could be that they may have decided not to develop that product. That's the most common reason, and I talked about that a little bit earlier, that that's happened over the years with ENHANZE. With regard to the specific statement on Hypercon, we really can't say any more about that. That program is actually progressing, and so we can't say more about that at this period of time.
But generally, it is if a product doesn't progress in the clinic or didn't achieve the efficacy profile that a partner would want. You may remember with our Bristol agreement, some of the earlier immunology, immune oncology targets that were more novel did not actually meet the clinical expectations, and BMS returned those targets when that was determined. That is the most common reason that we see.
The Hypercon team do not talk in terms of viscosity, but basically what I can say is we seek to have the injection strength be perhaps in the 40-50 newtons, which is the hand grip of a small child, as an example. Many of our drugs, that is easily injectable by an adult, as you can imagine. But many of the drugs in Hypercon we expect to be actually being given by auto-injector, which obviously can exert, and certainly the Halozyme auto-injectors have a lot more force that they can inject than that. What is remarkable about the Hypercon formulation is for the concentration, the ease with which it can be injected.
Your next question is from Mohit Bansal with Wells Fargo. Your line is now open. Please go ahead.
Hi, this is Chenxi from Mohit. Thanks for taking our question, and congrats on the quarter. I just have one question regarding 2027 and beyond. Shall we expect an update on the multi-year outlook in early next year as typical? I think you guys previously mentioned that the new three launches for ENHANZE, like, together contribute around 80%, grow about 80% sequentially in the second quarter. Just curious how much of that potential thousand [audio distortion] royalty step-down between 2029 and 2030 could be offset by these new launches? Then I have a follow-up question. Thank you.
Yeah, thanks for the question. We do plan to give 2027 guidance and an update on our long-range outlook when we report fourth quarter results in February. We remain very comfortable with the outlook and look forward to providing the update.
I think on the quarter-over-quarter growth and talking about the exciting new waves that we're seeing, we continue to see strong growth in those products. For each of those, there's a lot of growth left. I highlighted some of it in my call, but just to mention, OPDIVO Qvantig is about 17% converted today. Bristol expects it to be to 30%-40% over the next several years, and for that to continue, as we have seen, that moving to subQ is very sticky in terms of share.
For Ocrevus Zunovo, that's just at about 20% conversion today of what will be an $11 billion market, so very exciting there as well. RYBREVANT subQ, annualizing out to about $1.3 billion, but J&J has projected at least $5 billion in shares there. You're quite right in focusing on these being very meaningful contributors, but that's all the detail we can give you today.
Thank you. I just have another question regarding the collaboration revenues. I think you guys maintained the full-year guidance of $110 million-$130 million, versus roughly about $65 million so far has been kicked in. Shall we still expect the remaining revenue to be recognized in the fourth quarter, or has some of the portion of it will be shifted to 2027?
Always hard to predict exactly how the collaboration revenue is going to pan out, but we did guide to expect a little bit heavier weighting of that in the fourth quarter. I think you can expect to see some more coming in in fourth quarter.
Got it. Thank you.
We have reached the end of the Q&A session, which concludes today's call. Thank you so much for attending. You may now disconnect.